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Purpose: To review the characteristics, findings and quality of systematic reviews (SRs) on the effect of any vasopressor/inotrope on outcomes in adult patients with sepsis compared with either no treatment, another vasopressor or inotrope or fluids., Materials and Methods: We systematically searched Cochrane Central Register of Controlled Trials, PubMed and Embase (January 1993-March 2021). Descriptive statistics were used., Results: Among the 28 SRs identified, mortality was the primary outcome in most (26/28) and mortality was usually (23/28) studied using randomised controlled trials (RCTs). Fifteen SRs focused exclusively on patients with sepsis or septic shock. Sepsis and septic shock were always grouped for the analysis. Publication bias was consistently low when studied. The most consistent findings were a survival advantage with norepinephrine versus dopamine, which disappeared in analyses restricted to 28-day mortality, and more arrhythmias with dopamine. However, these analyses were dominated by a single study. Only 2 SRs were judged to be of moderate-high quality. Lack of blinding and attrition bias may have affected the outcomes., Conclusions: The quality of SRs on the effect of vasopressors/inotropes on the outcomes of adult patients with sepsis can be improved, but high-quality, multicenter, RCTs should be preferred to additional SRs on this topic., Competing Interests: Declaration of Competing Interest SE is associate editor of Intensive Care Medicine and a Cochrane Editor. AC is an advisory board member of Critical Care and an associate Editorial Board member of BJA. The other authors declare that they have no competing interests., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background: The best fluid replacement strategy and the role of albumin in immunocompromised patients with sepsis is unclear., Methods: We performed a secondary analysis of immunocompromised patients enrolled in the ALBIOS trial which randomized patients with severe sepsis or septic shock to receive either 20% albumin (target 30 g per liter or more) and crystalloid or crystalloid alone during ICU stay., Results: Of 1818 patients originally enrolled, 304 (16.4%) were immunocompromised. One-hundred-thirty-nine (45.7%) patients were randomized in the albumin while 165 (54.2%) in the crystalloid group. At 90 days, 69 (49.6%) in the albumin group and 89 (53.9%) in the crystalloids group died (hazard ratio - HR - 0.94; 95% CI 0.69-1.29). No differences were observed with regards to 28-day mortality, SOFA score (and sub-scores), length of stay in the ICU and in the hospital, proportion of patients who had developed acute kidney injury or received renal replacement therapy, duration of mechanical ventilation. Albumin was not independently associated with a higher or lower 90-day mortality (HR 0.979, 95% CI 0.709-1.352) as compared to crystalloid., Conclusion: Albumin replacement during the ICU stay, as compared with crystalloids alone, did not affect clinical outcomes in a cohort of immunocompromised patients with sepsis., Competing Interests: Declaration of Competing Interest AC, GG, JM, AM, MI, FT, CMB, SR, CAV, GB, RL, AG, AP, PC declare to have no competing interests., (Copyright © 2021. Published by Elsevier Inc.)

Purpose: To assess efficacy and safety of chloroquine (CQ)/hydroxychloroquine (HCQ) for treatment or prophylaxis of COVID-19 in adult humans., Materials and Methods: MEDLINE, PubMed, EMBASE and two pre-print repositories (bioRxiv, medRxiv) were searched from inception to 8th June 2020 for RCTs and nonrandomized studies (retrospective and prospective, including single-arm, studies) addressing the use of CQ/HCQ in any dose or combination for COVID-19., Results: Thirty-two studies were included (6 RCTs, 26 nonrandomized, 29,192 participants). Two RCTs had high risk, two 'some concerns' and two low risk of bias (Rob2). Among nonrandomized studies with comparators, nine had high risk and five moderate risk of bias (ROBINS-I). Data synthesis was not possible. Low and moderate risk of bias studies suggest that treatment of hospitalized COVID-19 with CQ/HCQ may not reduce risk of death, compared to standard care. High dose regimens or combination with macrolides may be associated with harm. Postexposure prophylaxis may not reduce the rate of infection but the quality of the evidence is low., Conclusions: Patients with COVID-19 should be treated with CQ/HCQ only if monitored and within the context of high quality RCTs. High quality data about efficacy/safety are urgently needed., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Purpose: COVID-19 (coronavirus disease 2019) is a public health emergency of international concern. As of this time, there is no known effective pharmaceutical treatment, although it is much needed for patient contracting the severe form of the disease. The aim of this systematic review was to summarize the evidence regarding chloroquine for the treatment of COVID-19., Methods: PubMed, EMBASE, and three trial Registries were searched for studies on the use of chloroquine in patients with COVID-19., Results: We included six articles (one narrative letter, one in-vitro study, one editorial, expert consensus paper, two national guideline documents) and 23 ongoing clinical trials in China. Chloroquine seems to be effective in limiting the replication of SARS-CoV-2 (virus causing COVID-19) in vitro., Conclusions: There is rationale, pre-clinical evidence of effectiveness and evidence of safety from long-time clinical use for other indications to justify clinical research on chloroquine in patients with COVID-19. However, clinical use should either adhere to the Monitored Emergency Use of Unregistered Interventions (MEURI) framework or be ethically approved as a trial as stated by the World Health Organization. Safety data and data from high-quality clinical trials are urgently needed., Competing Interests: Declaration of Competing Interest AC, GI, MI, AG, SE declare to have no competing interests., (Copyright © 2020 Elsevier Inc. All rights reserved.)